Bredemeier Maren, Edimiris Philippos, Mach Pawel, Kubista Mikael, Sjöback Robert, Rohlova Eva, Kolostova Katarina, Hauch Siegfried, Aktas Bahriye, Tewes Mitra, Kimmig Rainer, Kasimir-Bauer Sabine
Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.
TATAA Biocenter, Goeteborg, Sweden.
Clin Chem. 2017 Oct;63(10):1585-1593. doi: 10.1373/clinchem.2016.269605. Epub 2017 Aug 3.
Circulating tumor cells (CTCs) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTCs of MBC patients on the basis of the expression of 46 genes.
From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest (QIAGEN). Patients were grouped into (a) responder (R) and non-responder (NR) at TP1 and (b) overall responder (OR) and overall non-responder (ONR) at TP2. A 46-gene PCR assay was used for preamplification and high-throughput gene expression profiling. Data were analyzed by use of GenEx (MultiD) and SAS.
The CTC positivity was defined by the four-gene signature (, , , positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC- patients (, , , , , , , , , , , , , and ). was highly expressed in CTC+ patients and in the NR at TP1. A significant differential expression of 4 genes (, , , and ) was observed between OR and ONR when stratifying the samples into CTC+ or CTC-.
could be a key marker in distinguishing R from NR, and was powerful in identifying CTCs.
循环肿瘤细胞（CTC）被认为是监测转移性乳腺癌（MBC）疾病进展的理想替代标志物。我们基于46个基因的表达情况研究了MBC患者CTC对治疗反应的预测作用。
从45例MBC患者和20名健康供者（HD）中，在疾病进展时（TP0）以及连续2个临床分期时间点（TP1和TP2）采集2×5 mL血液，用于进行AdnaTest检测（QIAGEN公司）。患者在TP1时被分为（a）反应者（R）和无反应者（NR），在TP2时被分为（b）总体反应者（OR）和总体无反应者（ONR）。采用46基因PCR检测法进行预扩增和高通量基因表达谱分析。数据使用GenEx（MultiD）和SAS进行分析。
CTC阳性由四基因特征（、、、阳性）定义。确定了14个基因在CTC阳性和阴性患者之间存在显著差异表达（、、、、、、、、、、、、、和）。在TP1时，在CTC阳性患者中高表达，在NR中表达。将样本分为CTC阳性或阴性时，在OR和ONR之间观察到4个基因（、、、和）存在显著差异表达。
可能是区分R与NR的关键标志物，在识别CTC方面具有强大作用。
